We propose to establish a Clinical Center as part of the Hepatitis B Clinical Research Network (HB-CRN) consisting of three collaborating institutions in the states of Washington and Alaska. This Clinical Center brings together the patients, investigators, and resources of the University of Washington, including the University of Washington Medical Center, Children's Hospital and Regional Medical Center, Harborview Medical Center, and the Veterans Affairs Puget Sound Health Care System; Virginia Mason Medical Center; and, the Alaska Native Tribal Health Consortium, as well as a number of affiliated community and outreach clinics. The diversity and scope of our Clinical Center's participating institutions makes us confident that we can capture a large and heterogeneous cohort of HBV-infected patients in our region for inclusion in natural history studies and clinical trials of new therapeutic agents and approaches. We plan to establish a data base, a natural history study, and a biorepository of patients with chronic HBV infection from the Pacific Northwest and Alaska, including both adults and children from a diverse range of ethnic groups and encompassing 5 of the major HBV genotypes and several of the HBV sub-genotypes (A1, A2, Ba, Bj, C, D and F). We have included proposals for two potential studies: (1) a natural history study to elucidate the role of clinical, biochemical, and virologic factors on the transition between phases of chronic hepatitis B; and, (2) a clinical trial comparing combination therapy with tenofovir/emtricitabine versus monotherapy with tenofovir (in adults) or entecavir (in children) for the treatment of HBeAg positive patients with either immune active or immune tolerant disease.